Monoamine mediation of the morphine-induced activation of mice

1. The dose-response relationship for hyperactivity in grouped mice following the injection of morphine sulphate has been established.2. The activation response can be modified by drugs which affect either catecholamines or indoleamines.3. The monoamine precursors L-DOPA and 5-hydroxytryptophan potentiate the response.4. The monoamine synthesis inhibitors alpha-methyl-p-tyrosine and p-chlorophenylalanine reduce the response.5. Inhibition of monoamine oxidase activity by pargyline caused a great increase in the response. The simultaneous administration of reserpine resulted in a further potentiation.6. Reserpine blocked the response whenever it was given alone, either before, with or after the injection of morphine.7. Blockade of alpha-adrenoceptors with phentolamine or phenoxybenzamine reduced the response.8. Blockade of tryptaminergic receptors with methysergide or cinanserin also antagonized the response.9. The major tranquillizers haloperidol and chlorpromazine reduced the response. Haloperidol was especially effective in this regard.10. The tricyclic antidepressant drug imipramine potentiated the response.11. The morphine antagonist nalorphine completely prevented the response.12. The anticholinergic agent atropine and the antihistaminic drug mepyramine did not affect the response.13. We conclude that dopamine, noradrenaline and 5-hydroxytryptamine are all involved in the normal activation response of grouped mice to morphine, with dopaminergic mechanisms being of primary importance.